The long-term objective of this program is to understand the mechanism(s) of neoplastic transformation in cultured mammalian cells, particularly human cells. Studies described in this report address these intermediate goals: (1) modulation of proliferation and functional activity in epithelial cell cultures at determined calcium or dissolved oxygen concentrations; (2) assessment of the undersurface morphology of nonneoplastic and neoplastic cells by interference-reflexion microscopy; and (3) repair of DNA-protein crosslinks by normal human fibroblasts during inhibition of protein and DNA synthesis. Dissolved oxygen concentration is essential for continued proliferation and hemicyst formation by monkey kidney epithelial cells. Epithelial cells utilize oxygen rapidly and a means for maintenance of an adequate dissolved oxygen supply without a potentially deleterious excess is needed. Comparison of the undersurface of several rodent and human cells is in progress. Studies on the repair of nonlethal DNA-protein crosslinks reveal the potential for more than one pathway or mechanism of repair.